Progress in developing better knowledge in preventing and caring for hypertrophic scars has been hampered by lack of an appropriate animal model. Full thickness dermal destruction in mice heals by the process of wound contraction resulting in little scarring. The autosomal dominant mouse mutant, tight skin mouse, has been examined and found to heal skin wounds in the absence of wound contraction. In addition, developing scar tissue has a hypertrophic scar-like appearance based upon histological examination. This proposal plans to investigate healing, vascular architecture and collagen composition of tight skin mice and compare these histological, physiological and biochemical findings with normal litter mates. Preliminary results with mouse mutants demonstrate excess synthesis of granulation tissue and scarring in open wounds, alterations in vascular architecture with intact skin, and differences in solubility of collagens from granulation tissue and intact skin. Experimental conditions have been developed where wounds heal in the absence of wound contraction. Full thickness freeze wounds heal with no contraction. Preliminary studies using excised wounds in mutant mice, show wound contraction is impaired and wounds heal with hypertrophic-like scars. Studies are planned which will compare the effects of various injuries (excised, burn and freeze), on healing in mutant and normal mice. Gross and morphological differences will be compared between normal and mutant litter mates with variable types of injury. Other comparisons will examine possible differences in wound tensile strengths and vascular architecture of developing scars. Collagen typing, quantitation and structural composition will be studied in the two groups of mice. In vitro studies with mutant and normal cultured fibroblasts are in progress. Plans are presented for comparing synthesis of strucural protein made by these 2 cell lines. Mixing experiments are planned which will utilize the 2 cell lines incorporated into polymerized collagen matrix lattices constructed from either normal or mutant mouse puified collagens. These lattices will allow monitoring wound-like contraction in a controlled in vitro environment.